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Targeting of intracerebral functional regions has been limited by the inability to transport drugs across the blood-brain barrier (BBB) and by poor accumulation in these regions. To overcome these hurdles, liposomes modified with P-aminophenyl-α-d-mannopyranoside (MAN) were used as a fluorescent dye carrier through the BBB and used the specific distribution of liposomes (LIP) modified with MAN (MAN-LIP) to target various functional regions of the brain. An in vitro BBB model was established to evaluate the transendothelial ability of MAN-LIP, and liposomes uptake by C6 glioma cells was analyzed by flow cytometry and live cell imaging. Liposome targeting was evaluated using in vivo and ex vivo imaging. After MAN-LIP administration, the transendothelial ability and the delivery of fluorescent dye to the brain significantly increased. MAN-LIP concentrated in the cortex at 4 h, shifting distribution to the cerebellum and brainstem at 12 h. The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12 h. The results demonstrate that MAN-LIP is able to enhance cellular uptake in vitro and also promotes penetration through the BBB and accumulation in the brain with a distinct spatio-temporal pattern.

Respiratory syncytial virus (RSV) commonly infects the upper and lower respiratory tracts. Currently, there is no effective treatment available. Deoxyribozymes are a potential therapeutic for RSV and their activity is based on the ability to bind and cleave complementary RNA sequences to inhibit protein expression. DZ1133 is a deoxyribozyme that targets the conserved genomic RNA sequence of the RSV nucleocapsid protein and has been shown to significantly inhibit various strains of RSV including subgroups A and B, standard A2 and CH18537 strains, and CQ381513, CQ381170, BJ01 and BJ04 strains. Treatment with DZ1133 decreased viral plaque formation in lungs of RSV-infected BALB/c mice. In addition, viral mRNA expression was reduced, airway inflammation was alleviated, and leukocyte counts were reduced in bronchoalveolar lavage fluid of RSV-infected mice. The antiviral effect of DZ1133 was dose-dependent (0.2–0.8 mg) and more efficient than antisense oligonucleotide inhibition of gene expression. However, levels of cytokines TNF-α, IFN-γ, IL-12, and IL-10 induced by RSV infection were not affected by DZ1133 treatment. Our data demonstrate that DZ1133 is a potential therapeutic agent against both subgroups A and B RSV infection in vivo .

Respiratory syncytial virus (RSV) infection is ubiquitous and leads to various outcomes between immunocompetent and immunocompromised individuals. This study aimed to compare RSV infection and inflammatory responses between immunocompetent BALB/c mice and immunodeficient nude mice. RSV titers in both infected BALB/c mice and nude mice peaked on the third day post-inoculation, but the nude mice had longer lasting and higher levels of viral replication. RSV infection induced a more severe grade of pulmonary histopathology and larger numbers of leukocytes in airways of nude mice than that of BALB/c mice. RSV infection increased pulmonary macrophages and natural killer (NK) cells in both strains of mice. Furthermore, infected nude mice had larger numbers of pulmonary macrophages and NK cells than infected BALB/c mice. Whereas the RSV infected BALB/c mice secreted more tumor necrosis factor -alpha (TNF-alpha), interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and IL-10 than control BALB/c mice, the infected nude mice had higher levels of TNF-alpha, IL-12 and IL-10 than the infected BALB/c mice. The inflammation induced by RSV infection did not correspond with the immune response of T cells. Macrophages and NK cells were potent immunocytes and inflammatory cells in RSV infection especially when T lymphocytes were deficient. Therefore, nude mice may be a good model for severe and persistent RSV infection in immunocompromised hosts.

INTRODUCTION: Respiratory syncytial virus (RSV) infection is ubiquitous and leads to severe disease in immunocompromised individuals. OBJECTIVE: Our goal was to compare RSV infection and inflammation between immunocompetent BALB/c mice and immunodeficient nude mice. METHODS: Pulmonary viral titers, histology, immunohistochemistry for CD14 and CD56, leukocyte counting, and cytokines were assayed by enzyme-linked immunosorbent assay in bronchoalveolar lavage fluid. RESULTS: RSV titers peaked on the third day after inoculation in both types of infected mice. Infected nude mice had higher-level and more durative viral replication, more severe pulmonary histopathology, and a larger number of leukocytes in bronchoalveolar lavage fluid than infected BALB/c mice. Infected nude mice displayed more pulmonary (CD14+) macrophages (114.34 ± 20.24 vs 75.46 ± 12.37; P = .05) and (CD56+) natural killer cells (37.87 ± 8.07 vs 11.06 ± 5.37; P = .05) than infected BALB/c mice. RSV infection enhanced production of tumor necrosis factor α, interleukin 12 (IL-12), interferon γ, and IL-10 in both types of mice. Infected nude mice had a higher level of tumor necrosis factor α (40.30 ± 7.34 vs 24.24 ± 9.54; P = .05), IL-12 (83.96 ± 12.32 vs 68.21 ± 7.42; P = .05), and IL-10 (125.01 ± 18.97 vs 77.56 ± 9.01; P = .05) than infected BALB/c mice. CONCLUSIONS: RSV-infected nude mice are a good model for assessing severe and persistent infection in individuals at high risk. RSV-induced inflammation is not parallel to the immune response of T cells, and macrophages and natural killer cells contribute to severe infection and inflammation of RSV-infected cellular-immunodeficient individuals.